Fascioliasis or fasciolosis is a parasitary disease (helminthiasis) caused by two species of digenetic trematodes Fasciola hepatica and Fasciola gigantica, commonly known as liver flukes. These are localized in adults in biliary vesicle or in liver biliary ducts.
Fasciolosis causes large losses in livestock and in the economics of producing countries of domesticated animals and their products, such as milk, meat, wool, hide, etc. It also affects to cattle, sheep and goats, but it may be also present in wild animals, and sometimes in humans; therefore the infection is considered a zoonosis which is a severe worldwide problem.
Epidemiologic status of human fasciolosis has changed in recent years. Since 1980 the number of persons infected by Fasciola hepatica has significantly increased, and in several geographic zones true human endemics have been disclosed, with low to very high figures of prevalence and intensity. Prevalence zones for fasciolosis in humans do not necessarily match with zones wherein the disease constitutes a first order veterinary problem.
Fasciolosis may no longer be simply considered as a secondary zoonotic disease, but as a significant parasitic human disease (Bulletin of World Health Organization 1999, Mas-Coma). Fasciolosis is a global disease and human cases have been registered in more than 75 countries worldwide. Zones which are known for high transmission are South America highlands, Nile Valley, Caspian Sea basin extended between Europe and Asia, and also Eastern Asia, Southeastern Asia, United Kingdom and Australia. No country may be considered free from fasciolosis risk.
Forecast for fasciolosis incidence will be increasing in the future continuing with a trend noticed in recent years, such trend which is due to climate change (Van Dijk et al, 2010.). The disease has been diagnosed in 29 states within Mexico, wherein prevalence is in the range from 2% up to 100%. Data collected in Mexico show that among 36 million bovines, 18 million are exposed to infection by Fasciola hepatica, since cattle is located in zones known as “fasciolosis-relevant” (Ibarra, 2000).
Relevance of this parasitosis resides in such large economic losses caused to livestock, due to a generally chronic liver and bile conduct inflammatory process, and also due to digestive and nutritional disorders. That above is translated into direct losses due to death of young animals by massive infections of Fasciola hepatica, and indirect losses due to seizures of livers at slaughterhouse, abortions, low growth and reproduction rate and also low meat, milk production, predisposition to their diseases, and expenses by treatment.
The main compounds used for treatment of fasciolosis are shown in Table I, and their activity spectrum against trematode at several ages is summarized in Table II. (Fairweather and Boray 1999).
TABLE ITreatment with fasciolicidesCHEMICAL GROUPEXAMPLEHalogenated Bithionol (Bitin, Actamer), Hexachlorophene phenols(previously Bilevon, now obsolete), Niclofolan (Bilevon), nitroxynil (Trodax)SalycylanilidesBrotianide (dirian), Closantel (Flukiver, Seponver, Supaverm, Cosicare), Oxyclozanide (Nilzan, Zanil), Rafoxanide (Flukanide, Ranizole).BenzimidazolesAlbendazole (Valbazen), Mebendazole (Telmin, Vermox, Supaverm), Triclabendazole (Fasinex),Luxabendazole (Fluxacur).SulfonamidesChlorsulon (Curatrem, Ivomec F, Ivomec Plus).
TABLE IIEfficacy spectrum of drugs in recommended dose rates against Fasciola hepatica in sheep. FASCIOLA AGE IN WEEKSDRUG1234 5678910 11121314Bithionol,50-80-99%Hexachlorophene,70%Oxyclozanide,Niclofolan,Albendazole,Closulon +Ivermectin(injection)Closuron (oral)90-99%Nitroxynil,50-91-99%Closantel90%Rafoxanide50-91-99%90%Triclabendazole90-91-99%99%Diamphenetide91-100%50-80%
As noticed in above table II, albendazole, which was introduced in market in 1975, has been one of the most successful benzimidazole derivatives due to its high spectrum and high efficacy against gastrointestinal nematodes. However, it acts over Fasciola hepatica only on weeks 10-11, having a 50-70% efficacy; while in weeks 12-14 it shows 80-90% efficacy. Likewise, diamphenetide has 91 to 100% efficacy in 2-6 week juvenile fasciola, but not being effective in 7-week adult fasciola. The only fasciolicide acting in juvenile and adult stages is triclabendazole.
Recent studies demonstrate that in spite of the good fasciolicide activity features of orally administered triclabendazole, it has a significant drawback in being highly polar and very little soluble in biological fluids, as it is biotransformed in liver to form sulfoxide, this being a main metabolite showing fasciolicide activity, therefore being absorbed in only 5% of administered dose. In this context, triclabendazole is administered at a dose of 12 mg/Kg by weight in cattle, therefore 5400 mg of triclabendazole is needed for a 450 Kg bovine. Now, if 100 heads of cattle weighing an average of 450 Kg are available, 540,000 mg (540 g) of triclabendazole would be needed, and also when considered that only 5% is absorbed, then only 27 g of total administered weight to 100 heads of cattle would be absorbed, which represents a large loss in cost/profit.
As previously mentioned, plasma levels of triclabendazole as sulfoxide has been determined in other studies to be only of 5%, while the remaining is removed in feces (92%), in urine (2%) and in milk (1%), which pollute environment.
In spite of above, triclabendazole is still the drug of choice for treatment of liver trematode infections in cattle since almost 30 years, this being only orally administered.
Triclabendazole has been successfully used recently for treatment of fasciolosis in humans, showing high efficacy against adult and juvenile trematode located in biliary ducts and in liver parenchyma, respectively (Boray et al, 1983; (Smeal & Hall, 1983; Turner et al, 1984).
